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IND FAQ
What is an IND?
The Investigational New Drug (IND) application fulfills two regulatory requirements.
First, the application is through which a drug sponsor alters the FDA of its intentions to
conduct clinical studies with an investigational drug. The second purpose is a request for
an exemption from the federal statue that prohibits an unapproved drug from being
shipped in interstate commerce. In many ways, the IND application is the result of a
successful preclinical development program, and the vehicle the sponsor uses to advance
to the next stage.
What is the purpose of an IND?
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It affirms a body of knowledge about the manufacturing, pharmacology, and
toxicology of the drug to support its use in human testing
Requires that the clinical investigation be performed in accordance with Good
Clinical Practice (GCP)
Provides an additional level of protection through FDA oversight. The FDA’s
review focuses on safety of human subjects and ensuring that the studies will
produce useful information to assess safety and efficacy of the test product.
What is a drug?
Any substance that achieves its primary intended purposed through chemical action
within or on the body of man or other animal and is dependent upon being metabolized to
achieve its primary intended purpose.
The term "drug" means (A) articles recognized in the official United States
Pharmacopoeia, official Homoeopathic Pharmacopoeia of the United States, or official
National Formulary, or any supplement to any of them; and (B) articles intended for use
in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other
animals; and (C) articles (other than food) intended to affect the structure or any function
of the body of man or other animals; and (D) articles intended for use as a component of
any article specified in clause (A), (B), or (C). A food or dietary supplement for which a
claim, subject to sections 403(r)(1)(B) and 403(r)(3) or sections 403(r)(1)(B) and
403(r)(5)(D), is made in accordance with the requirements of section 403(r) is not a drug
solely because the label or the labeling contains such a claim. A food, dietary ingredient,
or dietary supplement for which a truthful and not misleading statement is made in
accordance with section 403(r)(6) is not a drug under clause (C) solely because the label
or the labeling contains such a statement.
Children’s Hospital Boston – Translational Research Program
Translational Research Program: www.childrenshospital.org/trp
Who is the Sponsor?
Sponsor means a person who takes responsibility for and initiates a clinical investigation.
The sponsor may be an individual or a pharmaceutical company, government agency,
academic institution, private organization, or other organization. The sponsor does not
actually conduct the investigation unless the sponsor is a sponsor-investigator.
Who is a Sponsor-Investigator?
Sponsor-Investigator means an individual who both initiates and conducts an
investigation, and under whose immediate direction the investigational drug is
administered or dispensed. A Sponsor-Investigator is required to fulfill the
responsibilities of both the Investigator and Sponsor.
Who is an Investigator?
An individual who actually conducts a clinical investigation, they are responsible for how
the test article is administered and/or dispensed to and in the event of an investigation
conducted by a team of individuals, is the responsible leader of that team.
What is FDA Form 1571?
The cover sheet for the Investigational New Drug Application - It is the responsibility of
a sponsor to complete the form FDA 1571. However, if the investigator is the IND
holder, she/he would have to assume the sponsor's responsibility, and therefore complete
the form.
What is FDA Form 1572?
Statement of Investigator - is a form that is completed by each investigator prior to
participating in an investigational new drug study. This form should be updated during
the course of an investigation if any information on the form changes.
Types of INDs
Investigator IND: an application submitted by a physician who both initiates and
conducts the investigation, and under whose immediate direction the investigational drug
is administered or dispensed.
Emergency Use IND: is a vehicle through which the FDA can authorize the immediate
shipment of an experimental drug for a desperate medical situation. Emergency use INDs
generally are reserved for life-threatening situations in which no standard acceptable
treatment is available and there is not sufficient time to obtained institutional review
Children’s Hospital Boston – Translational Research Program
Translational Research Program: www.childrenshospital.org/trp
board (IRB) approval. Emergency use INDs are also sometimes called “compassionate
use” or “single-patient” INDs.
Treatment IND: experimental drugs showing promise in clinical testing for serious or
life-threatening conditions are made widely available while the final clinical work is
performed and the FDA review takes place.
Screening INDs: this type is a subcategory of a commercial IND. In early phases of drug
development, before the development path is clear, exploratory studies may be conducted
on a number of closely related drugs to choose the preferred compound or formulation.
Usually the FDA requires a separate IND for each compound, but at this stage this type
of studies may be best and most efficiently conducted under a single IND.
What is a Phase I study?
Are studies which initially introduce an investigation new drug into humans. These
studies are designed to determine the metabolism and pharmacologic actions of the drug
in humans, the side effects associated with use of the drug, and if possible gain early
evidence on the effectiveness of the drug.
What is a Phase II study?
Are controlled clinical studies conducted to evaluate the effectiveness of the drug for a
particular indication(s) in subjects with the condition under study and to determine the
common short-term side effects and risk associated with use of the drug.
What is a Phase III study?
These are expanded studies which are performed after preliminary evidence suggesting
effectiveness of the drug has been obtained. There intended to gather the additional
information about effectiveness and safety that is needed that is needed to evaluate the
overall benefit-risk relationship of the drug and to provide an adequate basis for
physician labeling.
When can I start a clinical trial on my IND application?
The FDA is required by the Modernization Act to respond to an IND sponsor within 30
calendar days of receipt of a complete IND application. Unless you are contacted, you
may begin your study thirty days after FDA receives your IND application. The FDA
may grant approval, an exemption or place a Complete or Partial Clinical Hold to delay
the proposed clinical investigation. Holds may require modifications to the protocol and
resubmission. When a proposed study has been placed on hold, the investigational drug
may not be administered to research subjects.
No News = Good News
Children’s Hospital Boston – Translational Research Program
Translational Research Program: www.childrenshospital.org/trp
What if there is an amendment to your protocol?
Protocol amendments are necessary when a sponsor wants to change a previously
submitted protocol or to add a study protocol not submitted in the original IND.
For protocol amendments that introduce a new protocol should contain the protocol itself
along with a brief description of the most clinically significant differences between the
new and previous protocols.
Amendments that specify changes to previously submitted protocols are required when a
sponsor seeks: (1) Phase 1 modified in a manner that significant affects the safety of the
clinical subjects; or (2) a Phase 2 or 3 protocol modified in a manner that significant
affects the safety of the subjects; the scope of the investigation, or scientific quality of the
study.
PLEASE NOTE: All amendments still need to be submitted, reviewed and approved
by the IRB.
For additional information about IND protocol amendments please review the following
regulation on this topic (21 CFR Part 312.30):
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=312.30
What are IND Safety Reports?
Sponsors must submit IND safety reports to inform the FDA and all participating
investigators of any adverse event experience (AE) that is associated with the use of a
product and that is both serious and unexpected. The goal of this requirement is to ensure
the timely communication of the most important new information about experiences with
the investigational drug.
For additional information about IND safety reports please review the FDA regulation 21
CFR part 312.32:
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=312.32
What are the FDA requirements for pre-clinical studies?
Under FDA requirements, a sponsor must first submit data showing that the drug is
reasonably safe for use in initial, small-scale clinical studies. Depending on whether the
compound has been studied or marketed previously, the sponsor may have several
options for fulfilling this requirement: (1) compiling existing nonclinical data from past
in vitro laboratory or animal studies on the compound; (2) compiling data from previous
clinical testing or marketing of the drug in the United States or another country whose
population is relevant to the U.S. population; or (3) undertaking new preclinical studies
Children’s Hospital Boston – Translational Research Program
Translational Research Program: www.childrenshospital.org/trp
designed to provide the evidence necessary to support the safety of administering the
compound to humans.
During preclinical drug development, a sponsor evaluates the drug's toxic and
pharmacologic effects through in vitro and in vivo laboratory animal testing.
Genotoxicity screening is performed, as well as investigations on drug absorption and
metabolism, the toxicity of the drug's metabolites, and the speed with which the drug and
its metabolites are excreted from the body. At the preclinical stage, the FDA will
generally ask, at a minimum, that sponsors: (1) develop a pharmacological profile of the
drug; (2) determine the acute toxicity of the drug in at least two species of animals, and
(3) conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on
the proposed duration of use of the substance in the proposed clinical studies.
Children’s Hospital Boston – Translational Research Program